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CMAJ • November 28, 2000; 163 (11)
© 2000 Canadian Medical Association or its licensors

Research
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Hematologic dyscrasia associated with ticlopidine therapy: evidence for causality

Fran L. Paradiso-Hardy*, C. Mark Angelo§, Krista L. Lanctôt{dagger} and Eric A. Cohen{ddagger}

From *the Department of Pharmacy and the Divisions of Cardiology and Clinical Pharmacology, Sunnybrook & Women's College Health Sciences Centre, and the Faculty of Pharmacy, University of Toronto, Toronto, Ont.; {dagger}the HOPE Research Centre, Division of Clinical Pharmacology and Department of Psychiatry, Sunnybrook & Women's College Health Sciences Centre, and the Departments of Psychiatry and Pharmacology, University of Toronto, Toronto, Ont.; and {ddagger}the Division of Cardiology, Department of Medicine, Sunnybrook & Women's College Health Sciences Centre and University of Toronto, Toronto, Ont. §At the time of the study Mr. Angelo was a first-year chemical engineering student at the University of Toronto, Toronto, Ont.

Background: Several rare, potentially fatal types of hematologic dyscrasia, such as agranulocytosis, aplastic anemia, neutropenia, pancytopenia, thrombocytopenia and thrombotic thrombocytopenic purpura (TTP), have been associated with ticlopidine therapy. The extent to which ticlopidine is the causative factor has not been addressed quantitatively.

Methods: We identified 211 published case reports of hematologic dyscrasia associated with ticlopidine therapy from a MEDLINE search. We analyzed the 91 reports that could be evaluated, using the Bayesian Adverse Reaction Diagnostic Instrument to calculate the posterior probability that ticlopidine caused the hematologic dyscrasia based on epidemiologic and clinical trial data (prior odds) and case information (likelihood ratio).

Results: The median posterior probability values (and range) for agranulocytosis, aplastic anemia, neutropenia, pancytopenia, thrombocytopenia and TTP were 0.95 (0.53–0.98), 0.81 (0.57–0.93), 0.86 (0.75–0.96), 0.78 (0.61–0.89), 0.74 (0–0.92) and 1.0 (0.33–1.00) respectively. The posterior probability was 0.75 or greater in 82 (90%) of the case reports.

Interpretation: This systematic analysis provides stronger evidence to implicate ticlopidine as the causative factor in the various types of hematologic dyscrasia in most published case reports.




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T. A. Hutchinson
Bayesian assessment of adverse drug reactions
Can. Med. Assoc. J., November 1, 2000; 163(11): 1463 - 1464.
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